Measurements of tumor markers or tumor products are not sufficiently developed to differentiate between those patients with microscopic residual cancer who will develop tumor recurrence and therefore require adjuvant radiation and/or chemotherapy, from those patients who are cured as a result of their primary treatment and therefore do not require additional anti-cancer treatment. The potential of specific tumors to metastasize has been correlated with both the activation and inhibition of fibrinolysis. A new technique has been developed in our laboratory which allows easy quantitative evaluation of tumor inhibition of fibrinolysis. In addition, our laboratory has extensive experience utilizing a standard fibrin plate technique for evaluation of activators of firbrinolysis. Preliminary work from our laboratory has demonstrated a statistically significant relationship between tumor fibrinolytic activation/inhibition ratios and the presence of tumor metastases. The purpose of this project is to investigate the relationship between tumor interaction with the fibrinolytic system and tumor metastases. The areas of proposed investigation include the folowing: 1. correlation of tumor activation and inhibition of fibrinolysis and tumor activation/inhibition ratios with respect to the presence or absence of documented tumor metastases (clinical stage of the tumor); 2. evaluate tumor induced changes in the fibrinolytic system and the incidence of both venous and arterial thrombosis; 3. study the changes in tumor activation or inhibition of fibrinolysis and tumor activation/inhibition ratios with respect to the time course of tumor metastases in a biologically reproducible and predictible animal tumor model; 4. study the efficacy of adjunctive anti-cancer treatment with fibrinolytic, anticoagulant or anti-platelet agents in the animal tumor model utilized in section 3; 5. investigate the mechanism of tumor inhibition of fibrinolysis; and 6. study the changes in liver fibrinolysis which are associated with, but appear to precede, actual tumor implantation in the liver.